Maintaining proper electrolyte concentration in the human body is not normally a concern in a majority of healthy people, and does not typically receive a great amount of general attention. The healthy human body is able to maintain an electrolyte balance within appropriate limits.
When, due to sudden illness, chronic illness, extreme diet, or medication, electrolytes become unbalanced, the result can be fatal. For example, when blood potassium concentration drops below a lower threshold, cardiac arrhythmia can occur, which can lead quickly to cardiac arrest and sudden death.
Heart failure is a chronic condition, in which the heart mechanically deteriorates over time. Heart failure can often be initiated by a non-fatal heart attack that kills cardiac muscle tissue, resulting in a weaker heart. The weaker heart does not pump as much blood with each stroke, leading to the heart enlarging to compensate in volume for the lack of strength.
The reduced pumping action of the heart can cause fluid to accumulate in the body, particularly in the extremities. In order to reduce the amount of fluid accumulation, heart failure patients are often prescribed diuretics, which reduce the amount of water maintained in the body. Diuretics work by regulating the excretion of water from the body through the kidneys. Increased water voiding reduces the amount of water held in the body, but can also increase the amount of potassium excreted, thereby decreasing the potassium concentration in the patient's blood. As previously described, low potassium levels can prove fatal.
Kidney disease patients may also be prescribed medications that alter the electrolyte balance. Even if not taking medication, patients having kidney problems may benefit from having electrolyte balance monitored. Examples of patients that would benefit from improved electrolyte monitoring include heart failure patients on ACE inhibitors and diuretics, hypertension patients, diabetes patients, kidney failure patients, and patients on dialysis.
Current patient management techniques may include visits to physicians or lab every other day to draw blood and measure electrolytes. Some single use, at home tests that require drawing blood (e.g. finger sticks) also exist. Applicant is not aware of any implantable, continuous potassium sensors currently available.
Many current cardiac rhythm management (CRM) products might be improved if biochemical sensors were incorporated, to either optimize the therapy or to measure physiologic variables for diagnostic purposes. In one example, related to heart failure, it has been found that the risk of both morbidity and death among patients with severe heart failure is reduced substantially, when aldosterone receptor antagonist-spironolactone is added to standard drug therapy (in conjunction with an ACE inhibitor and/or a loop diuretic). Higher doses of spirinolactone is needed to treat severe heart failure conditions. However, the higher the spirinolactone dose, the higher the risk of hyperkalimia. Thus it would be highly desirable to have an in vivo K+ sensor to optimize spirinolactone dosing. In addition, if sensors were available for both Na+ and K+ to monitor kidney function, it would benefit heart failure disease management significantly, since the kidney is the main organ regulating body fluid excretion and balance.
Ion-selective electrodes (ISEs) have long been used to measure ion concentrations. One well-known ISE is a hydrogen ISE, typically known as a pH electrode. Other ISEs are also well known and commercially available. For example, ISEs exist which are selective for sodium ions. Sodium ISEs can be used on a bench top to measure sodium concentration in blood.
Electrochemical potentials are associated with electrochemical half-cell reactions. The half-cell reactions each have a potential relative to that of a standard half cell. Potentiometric ion-selective electrodes do not function by measuring absolute electrical potential. Rather, the ISE (the working electrode) and another electrode (the reference electrode) are coupled as a pair, and the differential electrical potential between the two is used as an indication of ion activity near the ISE.
The reference electrode used with an ISE is often a Ag/AgCl (metal/metal halide) electrode immersed in a saturated KCl solution, at defined concentration, pressure, and temperature. The KCl solution may in turn be immersed in, and in fluid communication with another solution, a salt bridge. The KCl can be depleted over time, and the KCl refilled through a port in the reference electrode designed for that purpose. The size of the KCl reservoir can be reduced, with an attendant reduction in time between required refills. This reference electrode is typically quite large, complicated to fabricate, and prone to drift in potential caused by samples and environment.
Current reference electrodes are thus not optimally suited for long term implantation. Applicant believes that both the reference electrode size and refill requirement has posed significant challenges to develop implantable ISEs, due to the need for a reference electrode, and the current lack of suitable implantable reference electrodes.
What would be desirable are small ISE electrode pairs suitable for implantation into a human body that do not require a conventional reference electrode.